The HIV is a retrovirus with RNA-type genetic information. As the medical treatment agents of the virus, there are reverse transcriptase inhibitors and HIV protease inhibitors, etc. However, since almost all the inhibitors are only capable of preventing an infection of cell but not capable of preventing the virus duplication in an infected cell, the inhibitors are generally known as an inhibitor for extending a life span of human slightly rather than curing the disease. Due to the development of a certain virus having tolerance to the compounds, a new curative medicine with a new structure is urgently needed.
The HIV protease inhibitors developed so far are Saquinavir of the Roche company (European Patent 432695 A (1991)), Amprenavir of the Glaxo-Wellcome company (U.S. Pat. No. 941,982 (1992)), Indinavir of the Merck company (U.S. Pat. No. 789,508 (1991)), Ritronavir of the Abbott company (U.S. Pat. No. 998,114 (1992)), and Nelfinavir of the Agouron company (U.S. Pat. No. 5,484,926 (1996)). The compounds are mainly used for treating or preventing the acquired immune deficiency syndrome (AIDS) due to HIV infection.
The HIV protease inhibitors are belonging to an inhibitor referred as a hydroxyethylamine family. The compounds except for Nelfinavir, i.e., Saquinavir, Palinavir and Amprenavir have a benzyl group at the second carbon position in the structure of hydroxyethylamine.
As the intermediates for the synthesis of the HIV protease inhibitor, (2R)-[1′(S)-azido-2-phenylethyl]oxiran (J. Med. Chem. 1993, 36, 292–294), 3(S)-amino-1,2(S)-epoxy-4-phenylbutane, etc. have been known. Since the intermediates are prepared from phenylalanine, they always have benzyl groups at the structure of hydroxyethylamin (HEA). However Nelfinavir has a phenylthiomethyl group instead of a benzyl at HEA, a intermediates with different structures such as 3(S)-amino-1,2(S)-epoxy-4-phenylbutane is necessary.
Therefore, in order to develop a conventional or new HIV protease inhibitor, new intermediates capable of accepting a benzyl group as well as phenylthiomethyl or other substituents are necessary.